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Inhibiting effects of cytokine-induced killer cells co-cultured with hepatoma target peptide-sensitized dendritic cells on hepatoma cancer: Preliminary observations in vitro and in nude mice
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Abstract:
Objective : To investigate the effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) challenged with hepatoma target peptides on hepatoma cancer cell growth in vitro and in nude mice in vivo . Methods: Peripheral blood mononuclear cells (PBMCs), isolated from healthy volunteer subjects, were induced to differentiate into DCs and CIK cells with different cytokines, respectively. DCs were then stimulated with target peptides or whole cell lysates from human hepatoma HuH-7 cells to develop into DC HuH-7 or DC target which were co-cultured with CIK cells for 6 days to obtain DC HuH-7-CIK or DC target-CIK cells. Concentrations of IL-12 and INF-γ produced by CIK cells, DC-CIK cells, DC HuH-7-CIK or DC target-CIK cells were measured by ELISA. The cytotoxicity of these four types of effector cells against HuH-7 cells respectively was evaluated by CCK-8 assays in vitro and by HuH-7 cell transplantation assays in nude mice in vivo . Results: IL-12 production was significantly increased ( P <0.01) in DC HuH-7-CIK cells (179.33±14.04 pg/ml) and DC target-CIK cells (173.33±6.66 pg/ml) as compared with DCs (59.33±11.84 pg/ml). Similarly, IFN-γ production was significantly increased in CIK cells co-cultured with DC HuH-7 or DC target ( P <0.01) but was not significantly different between DC HuH-7-CIK and DC target-CIK cells ( P >0.05). Compared with untreated CIK cells, DC HuH-7-CIK cells and DC target-CIK cells possessed a similarly higher cytotoxic activity against HuH-7 cells in vitro ( P <0.05) and a similarly stronger inhibitory effect on tumor growth in nude mice bearing hepatoma cancer (\[5469±28.07\] vs \[78.48±1458\]% and \[85.78±15.69\]% respectively, P <0.05). Conclusion: Hepatoma target peptides-sensitized DCs may significantly enhance the cytotoxicity of CIK cells against human hepatoma cells, thus offering a potential strategy to enhance cell-based immunotherapy for liver cancer.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81001106)
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